Flexibility and plasticity in neuronal signalling is a property of the central nervous system, which allows the individual to adapt to its surroundings and to change its behavior according to past experience. Those electrophysiological phenomena in which the response of a stimulated pathway is modified by its preceding activity are likely to underlie the neuronal plasticity. An example of such a phenomenon is postactivation potentiation, which is characterized by an increase in the neuronal activity to a single stimulus following a brief intense synaptic stimulation. The dentate fascial (of the hippocampal formation) following brief tetanic stimulation of its afferent pathway (the perforant path), yields potentiation lasting for hours, even days. The time course makes the potentiation comparable to the duration of a learned response. In view of the possibility that postactivation potentiation and memory formation may have a common mechanism, we studied with the electron microscope morphological changes on synapses in the dentate fascia in the course of postactivation potentiation. Results of these experiments showed a considerable swelling (by 60%) of the dendritic spines in the region of the dentate fascia where the perforant path terminates. An increase in the volume of the spine will decrease the length resistance of the spine and hence its length constant, which in turn will enhance the electrotonic spread of the synaptic current. Consequently, the chance that the neuron will discharge becomes greater. The degree and the location of the poststimulation morphological change points to a causal rather than a coincidental relation between the spine swelling and postactivation potentiation. It is proposed to bring further evidence on the causal relation between these two phenomena by demonstrating they both have a comparable time course. In order to understand the mechanism of the spine swelling, an attempt will be made to suppress the latter pharmacologically. If the spine swelling were the common mechanism of potentiation and memory, then it should also occur in the process of learning. Therefore, this proposal is ultimately aimed at the demonstration of morphological changes underlying certain phases of the process of learning and memory.